Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy
Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy
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胰岛素恢复糖尿病性胃病中丧失的神经元一氧化氮合酶表达和功能
DOI：
10.1172/jci8273c1
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Ferris,CD
中科院分区：
文献类型：
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作者：
Watkins,CC;Sawa,A;Jaffrey,S;Blackshaw,S;Barrow,RK;Snyder,SH;Ferris,CD
胃肠道功能障碍在糖尿病患者中很常见。在小鼠糖尿病的遗传（非肥胖糖尿病）和毒素诱导（链脲霉素）模型中，我们发现胃排空和幽门肌的非肾上腺素能、非胆碱能松弛的缺陷，类似于神经元一氧化氮合酶基因（nNOS）缺失的小鼠的缺陷。糖尿病小鼠幽门nNOS蛋白和mRNA明显降低。糖尿病小鼠nNOS的下降不是由于肌间神经元的丧失。经胰岛素治疗后，nNOS表达及幽门功能恢复正常。因此，小鼠的糖尿病性胃病反映了胰岛素敏感的可逆性nNOS丧失。在糖尿病动物中，胃排空延迟可以用磷酸二酯酶抑制剂西地那非逆转。这些发现对新的治疗方法具有启示意义，并可能阐明糖尿病胃病的病因。
Gastrointestinal dysfunction is common in diabetic patients. In genetic (nonobese diabetic) and toxin-elicited (streptozotocin) models of diabetes in mice, we demonstrate defects in gastric emptying and nonadrenergic, noncholinergic relaxation of pyloric muscle, which resemble defects in mice harboring a deletion of the neuronal nitric oxide synthase gene (nNOS). The diabetic mice manifest pronounced reduction in pyloric nNOS protein and mRNA. The decline of nNOS in diabetic mice does not result from loss of myenteric neurons. nNOS expression and pyloric function are restored to normal levels by insulin treatment. Thus diabetic gastropathy in mice reflects an insulin-sensitive reversible loss of nNOS. In diabetic animals, delayed gastric emptying can be reversed with a phosphodiesterase inhibitor, sildenafil. These findings have implications for novel therapeutic approaches and may clarify the etiology of diabetic gastropathy.